Shigeno K, Nakamura T, Inoue M, Ueda H, Kobayashi E, Nakahara T, Lynn A K, Toba T, Yoshitani M, Fukuda S, Kawanami R, Shimizu Y
Department of Bioartificial Organs, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
Int J Artif Organs. 2002 Nov;25(11):1095-102. doi: 10.1177/039139880202501109.
Alveolar bone resorption and atrophy of the mandible are a major challenge for regeneration medicine. In the present investigation, a collagen sponge that contained TGF-beta1 was placed at a mandibular defect and the osteogenic effects of collagen-TGF-beta1, complex were evaluated.
The Pm2, Pm3, and Pm4 teeth on both sides of the mandibles of 12 adult beagle dogs (9.0-12.0 kg) were extracted. After the extraction-site wounds healed, a bone defect (10.0 x 15.0 mm-wide, 10.0 mm-deep or 10.0 x 10.0 mm-wide, 10.0 mm-deep) was created on the mandible. A collagen sponge (10.0 x 10.0 x 10.0 mm) that contained TGF-beta1 (1.0 microg, 5.0 microg, or 10.0 microg, in physiological saline) was placed at the bottom of the defect and the overlying mucous membrane was sutured with 4-0 prolene. As a control, a collagen sponge that contained physiological saline only was placed in a defect on the opposite side. Two weeks after the surgery the wounds above the bone defects on both the control and TGF-beta1-treated sides had healed completely.
At four, six, or eight weeks post-operatively animals were killed. Soft X-ray and bone-salt measurement analyses confirmed clearly that there was greater calcified bone formation in the defects into which TGF-beta1 had been incorporated than with the control defects. The implanted collagen sponges were fully resorbed and the bone tissue had regenerated from the bottom of the defects on the TGF-beta1, side by four weeks. On the control side, no such regeneration was observed.
These results indicate that TGF-beta1, released slowly from a collagen sponge was effective in promoting bone remodeling when applied to mandibular defects in adult dogs.
牙槽骨吸收和下颌骨萎缩是再生医学面临的重大挑战。在本研究中,将含有转化生长因子β1(TGF-β1)的胶原海绵置于下颌骨缺损处,评估胶原 - TGF-β1复合物的成骨作用。
选取12只成年比格犬(体重9.0 - 12.0 kg),拔除双侧下颌的第二前磨牙、第三前磨牙和第四前磨牙。拔牙创口愈合后,在下颌骨上制造骨缺损(宽10.0×15.0 mm、深10.0 mm或宽10.0×10.0 mm、深10.0 mm)。将含有TGF-β1(1.0微克、5.0微克或10.0微克,溶于生理盐水)的胶原海绵(10.0×10.0×10.0 mm)置于缺损底部,用4-0普理灵缝线缝合覆盖的黏膜。作为对照,在对侧缺损处放置仅含生理盐水的胶原海绵。术后两周,对照组和TGF-β1处理组骨缺损上方的创口均已完全愈合。
术后4周、6周或8周处死动物。软X线和骨盐测量分析清楚地证实,与对照缺损相比,植入TGF-β1的缺损处有更多的钙化骨形成。植入的胶原海绵完全吸收,到4周时,TGF-β1侧缺损底部已再生出骨组织。而在对照侧,未观察到这种再生。
这些结果表明,当应用于成年犬的下颌骨缺损时,从胶原海绵中缓慢释放的TGF-β1能有效促进骨重塑。